Stress and immunosuppression

Environmental stressors reportedly affected approximately 25 cetacean, three seal, and 21 fish species (Weilgar, Reference Weilgar2007; Warner, Reference Warner2008; Wang, Reference Wang2009). In cetaceans, environmental stressors stimulate the hypothalamic–pituitary–adrenal (HPA) axis, regardless of age (Wright et al., Reference Wright, Soto, Baldwin, Bateson, Beal, Clark, Deak, Edwards, Ferandez, Godinho, Hatch, Kakuschke, Lusseau, Martineau, Romero, Weilgart, Wintle, Notarbartolo-di-Sciara and Martin2007; Rolland et al., Reference Rolland, Parks, Hunt, Castellote, Corkeron, Nowacek, Wasser and Kraus2012). Such stressors are directly and positively correlated with glucocorticoid secretions (Romano et al., Reference Romano, Keogh, Kelly, Feng, Berk, Schlundt, Carder and Finneran2004; Rolland et al., Reference Rolland, Parks, Hunt, Castellote, Corkeron, Nowacek, Wasser and Kraus2012). The activation of the HPA-axis is a classic endocrine response to environmental stressors. Stress stimulates the secretion of corticotrophin-releasing hormone from the hypothalamus, which further acts on the pituitary to secrete the adrenocorticotrophic hormone and glucocorticoids from the adrenal cortex. Secretion of glucocorticoids further stimulates gluconeogenesis to provide energy to cope with stressful situations (Whirledge and Cidlowski, Reference Whirledge and Cidlowski2010). Higher glucocorticoid in response to stress is essential for maintaining physiologic integrity and ultimately the survival of an organism (Ulrich-Lai and Herman, Reference Ulrich-Lai and Herman2009). However, if the stressor persists for a long period, or if the intensity of the stressor is high, consequences to the animal could occur. The chronic or potent stress response causes the secretion of higher adrenal corticosteroids, which suppresses the immune system of an individual and puts the individual at risk of infection with various environmental pathogens (Shelley, Reference Shelley2014).

In response to inflammation or an infection, the activation of HPA-axis and the central noradrenergic stress system by various cytokines and other mediators is a key pathophysiological adaptation (Chrousos, Reference Chrousos1995; Nylen and Müller, Reference Nylen and Müller2004; Schuetz and Müller, Reference Schuetz and Müller2006; Müller, Reference Müller2007). The appropriate activation of the HPA-axis is crucial for survival of an animal. Activation improves the hemodynamic status, acute provision of energy, and defense against an excessive inflammation response (Van den Berghe et al., Reference Van den Berghe, de Zegher and Bouillon1998; Marik et al., Reference Marik, Kiminyo and Zaloga2002). It is difficult to investigate a direct link between the immune system and stress because there are many alternative indirect pathways through which a glucocorticoid response could be functional (Shelley, Reference Shelley2014). Some of these factors include metabolic rate, nutrient distribution, malnutrition, tissue catabolism, altered maturation, activity level, temperature changes, and disruption of circadian rhythms (Moberg, Reference Moberg1985). Stress has been reported to reduce monocytes (O'Connor et al., Reference O'Connor, O'Halloran and Shanahan2000), suppress natural killer cell activity, and to induce lympholysis through apoptosis (O'Connor et al., Reference O'Connor, O'Halloran and Shanahan2000). It has been suggested that immune cell differentiation could be altered in chronically stressful situations in which endogenous glucocorticoid production is high (Rook et al., Reference Rook, Hernandez-Pando and Lightman1994). Glucocorticoids quantitatively reduce the immune reaction through decreased antibody response and inhibited enzyme production. There are also reports of diminished production of interleukin-1 (IL-1), a soluble cytokine produced in the initial phases of macrophages responses, which stimulates T-cell proliferation (Wolkow et al., Reference Wolkow, Aisbett, Reynolds, Ferguson and Main2015). I has a crucial role in immunoregulatory mechanisms (Garlanda et al., Reference Garlanda, Dinarello and Mantovani2013). More information is undoubtedly forthcoming as to whether glucocorticoids have an ongoing immunoregulatory role via this mechanism (Cain and Cidlowski, Reference Cain and Cidlowski2017).

Glucocorticoids can also cause thymic involution. Necropsy of stressed or glucocorticoid-treated rats has shown a marked reduction in the weight and size of the thymus. The destroyed thymocytes are not immunocompetent, and most will not mature or reach the blood circulation. Thymic involution is caused by a direct lytic effect of glucocorticoids on thymocytes, which results in the activation of spontaneous cellular death that generally happens in this tissue as opposed to the induction of necrosis. Thymic involution is diagnostic of stress-induced immunosuppression and is much more prominent in young and female animals (Rosenberg and Lysz, Reference Rosenberg and Lysz1980; Moberg, Reference Moberg1985).

Glucocorticoids influence various immune parameters systemically decreasing lymph node and spleen mass, as well as thymic involution, and leukopenia. Glucocorticoids also influence plasminogen interleukin production, lymphocyte mitogen response, primary/secondary antigen response, IgA, IgM, IgE, mixed-leukocyte-response IgG, and monocyte function (Moberg, Reference Moberg1985). In such immunocompromised animals, various opportunistic pathogens become active and can cause infections (Reeb et al., Reference Reeb, Best, Botha, Cloete, Thornton and Mouton2010). The information about the link between stress and immunity comes from other vertebrates. Therefore, detailed knowledge is required to investigate the direct link between various stressors and immune system in cetaceans under control conditions.

Stress and pneumonia

When marine mammals are exposed to chronic and persistent stressors, and the animals are unable to adapt, negative effects on the animal's immune, metabolic, reproductive, and psychologic systems can occur (St. Aubin and Dierauf, Reference St. Aubin, Dierauf, Dierauf and Gulland2001). With a compromised immune system, the animal is more vulnerable to various infectious diseases which could potentially lead to the development of a pathological condition (St. Aubin and Dierauf, Reference St. Aubin, Dierauf, Dierauf and Gulland2001). Stress can be induced in both free-ranging and captive marine mammals exposed to a series of events such as food competition, environmental degradation, fishing, parasitism, overcrowding, isolation, predation, capture boats heavy traffic, excessive noise, social environment, transportation, or inadequate facilities (St. Aubin and Dierauf, Reference St. Aubin, Dierauf, Dierauf and Gulland2001; Van Bressem et al., Reference Van Bressem, Raga, Di Guardo, Jepson, Duignan, Siebert, Barrett, Santos, Moreno, Siciliano, Aguilar and Van Waerebeek2009). During stress, alteration in the respiratory tract of the microbial flora occurs (St. Aubin and Dierauf, Reference St. Aubin, Dierauf, Dierauf and Gulland2001). If animals are exposed for a long time to various nutritional, environmental, physiologic, and immune-altering conditions, some members of the normal microbiota will become opportunistic pathogens and cause disease (Tlaskalová-Hogenová et al., Reference Tlaskalová-Hogenová, Stepánková, Hudcovic, Tucková, Cukrowska, Lodinová-Zádníková, Kozáková, Rossmann, Bártová, Sokol, Funda, Borovská, Reháková, Sinkora, Hofman, Drastich and Kokesová2004). Even chlorine and other antimicrobial chemicals added to water can alter normal microbiota which can negatively affect immunosuppressed individuals (Buck, Reference Buck1980).

Most importantly, bacterial pneumonia is the most common cause of death in captive dolphins (Eo and Kwon, Reference Eo and Kwon2011), orcas (Rozanova et al., Reference Rozanova, Alekseev, Abramov, Rassadkin and Shestopalov2007) and in wild and stranded animals (Domiciano et al., Reference Domiciano, Domit, Broadhurst, Koch and Bracarense2016). Similarly, in British water dolphins (Baker, Reference Baker1992) and harbor porpoises, bacterial pneumonia was also the most common cause of death (Baker and Martin, Reference Baker and Martin1992). Therefore, bacterial pneumonia seems to be a common problem for both captive and wild cetaceans (Dunn, Reference Dunn and Dierauf1990). The respiratory system is well defended against bacterial pathogens which are inhaled by alveolar macrophages, monocytes and neutrophils, antimicrobial peptides, mucociliary clearance, and proinflammatory responses of the respiratory epithelium. However, these defenses can be compromised due to stress, glucocorticoids, poor air quality, and abrupt exposure to cold air and viral infections. When these defenses fail, the lungs can be colonized by bacterial pathogens that are capable of causing pneumonia (Caswell, Reference Caswell2013). It has been reported that the release of stress hormones has detrimental effects on the immune system (Reiche et al., Reference Reiche, Morimoto and Nunes2005; Marketon and Glaser, Reference Marketon and Glaser2008) and the growth and virulence of bacteria (Freestone et al., Reference Freestone, Sandrini, Haigh and Lyte2008). It has been suggested that the stress hormone status of the host could determine the outcome of an infection (Freestone et al., Reference Freestone, Sandrini, Haigh and Lyte2008). Some bacteria can recognize the release of stress hormones by the host. These hormones act as an environmental cue to initiate growth and pathogenic processes (Sandrini et al., Reference Sandrini, Fayez, Primrose and Hasan2014). The growth of several bacteria species such as Pseudomonas aeruginosa, Bordetella bronchiseptica, Campylobacter jejuni, Salmonella typhi, and Escherichia coli has been reported to be augmented by the release of catecholamine (Sharaff and Freestone, Reference Sharaff and Freestone2011).

Chemical pollution and pneumonia

Due to their aquatic nature, cetaceans accumulate the highest levels of environmental contaminants, especially heavy metals, organochlorine pesticides (OCPs), and polychlorinated biphenyls (PCBs). Toxins can affect the immune system of marine mammals in several different ways such as hematology/circulating immune cell populations, cytokine gene expression, immunoglobulin production, and cytotoxicity. Long-term exposure to such immunotoxic pollutants may have significant population-level consequences to marine mammals in the form of infectious disease outbreaks (Desforges et al., Reference Desforges, Sonne, Levin, Siebert, De and Dietz2016). Similarly, oil spills in the aquatic environment are associated with chronic lung infections in marine mammals (Pasamontes et al., Reference Pasamontes, Aksenov, Schivo, Rowles, Smith, Schwacke, Wells, Yeates, Venn-watson and Davis2017). A histopathological study of lung samples from marine otters (Lontra felina), Burmeister's porpoises (Phocoena spinipinnis), dusky dolphins (Lagenorhynchus obscurus), bottlenose dolphins (Tursiops truncatus), striped dolphins (Stenella coeruleoalba), and South American sea lions (Otaria flavescens) indicated that all of these animals had pneumonia. This may have contributed to or was the primary cause of stranding of these cetaceans (Gonzales-Viera et al., Reference Gonzales-Viera, Chavera, Yaipén-Llanos and Perales-Camacho2011; Grattarola et al., Reference Grattarola, Giorda, Iulini, Pautasso, Ballardini, Zoppi, Marsili, Peletto, Masoero, Varello, Garibaldi, Scaglione, Di Guardo, Dondo, Goria, Serracca, Mignone and Casalone2018). Various pollutants such as mercury, selenium, and zinc have been found at significantly higher levels in porpoises that died of pneumonia compared to those that died from physical injuries (Siebert et al., Reference Siebert, Joiris, Holsbeek, Benke, Failing, Frese and Petzinger1999; Bennett et al., Reference Bennett, Jepson, Law, Jones, Kuiken, Baker, Rogan and Kirkwood2001). Unfortunately, the Yangtze and Indus Rivers are highly polluted by urban sewage, agricultural effluents, industrial discharge, and ship navigation wastes (World Bank, 2005; Floehr et al., Reference Floehr, Xiao, Scholz-Starke, Wu, Hou, Yin, Zhang, Ji, Yuan, Ottermanns, Roß-Nickoll, Schäffer and Hollert2013). Such water pollution in rivers and lakes are a grave threat to the local biodiversity (Lu et al., Reference Lu, Xie, Zhou, Zhang and Liu2008). Approximately, 106 hazardous organic chemicals have been detected in sediments and 206 in the water from the Yangtze River (Wang and Peng, Reference Wang and Peng2002). These chemical pollutants include persistent organic pollutants (Ritter et al., Reference Ritter, Solomon and Forget1995), polycyclic aromatic hydrocarbons, benzo(a)pyrene, OCPs, PCBs (Floehr et al., Reference Floehr, Xiao, Scholz-Starke, Wu, Hou, Yin, Zhang, Ji, Yuan, Ottermanns, Roß-Nickoll, Schäffer and Hollert2013), polybrominated diphenyl ethers (Shen et al., Reference Shen, Yu, Zheng, Yu, Lam, Feng and Wei2006), phthalic acid esters (Wang et al., Reference Wang, Sha, Xia and Liu2008a, Reference Wang, Frasier, Yang and Whiteb), perfluorinated compounds (Jin et al., Reference Jin, Ding, Zhai, Wang, Dong and Shu2006), and nonylphenol and bisphenol A (Shao et al., Reference Shao, Hu, Yang, An and Tao2005). Similarly, in the Indus River of Pakistan, about 90% of the municipal and industrial wastes enter the river and its adjoining lakes (World Bank, 2005). The most common pollutants found are copper, cadmium, arsenic, mercury, and lead (Gachal et al., Reference Gachal, Slater, Qadri, Nisa and Zuhra2006a, Reference Gachal, Slater, Nisa and Qadrib; Humerah et al., Reference Humerah, Munazza and Sheikh2011; Afzal et al., Reference Afzal, Shaukat, Zafar and Abbas2012).

Pneumonia-caused mass mortalities in marine mammals

Several bacterial species from four phyla (Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria), including Providencia rettgeri, Staphylococcus sciuri, P. aeruginosa, Kerstersia gyiorum, Aeromonas hydrophila, Elizabethkingia spp., Achromobacter spp., Streptococcus dysgalactiae, Acinetobacter lwoffii, Pseudomonas veronii, and Rothia spp., have been reported in the captive YFPs blowhole samples. The low bacterial diversity in the captive blowhole samples might be due to the good hygienic condition (Wan et al., Reference Wan, Richard, Junying, Yujiang, Jinsong and Ding2016). The bacterial phyla Proteobacteria, Firmicutes, and Bacteroidetes found in the YFPs are also commonly found in the respiratory tract of the bottlenose dolphin (Morris et al., Reference Morris, Johnson, Pisani, Bossart, Adams, Reif and Fair2011) and manatees (Trichechus manatusmanatus) (Vergara-Parente et al., Reference Vergara-Parente, Sidrim, de Pinho Pessoa, Parente, Marcondes, Teixeira and Rocha2003). However, the Actinobacteria found in the YFPs is not commonly reported in the respiratory system of bottlenose dolphins (Johnson et al., Reference Johnson, Torralba, Fair, Bossart, Nelson and Morris2009). Like YFPs, P. aeruginosa has been isolated frequently from the respiratory system of different aquatic mammals, such as whiteside dolphins (Lagenorhynchus acutus) (Buck et al., Reference Buck, Bubucis and Spotte1988), belugas (Delphinapterus leucas) (Dunn et al., Reference Dunn, Buck and Robeck2001), and bottlenose dolphins (T. truncatus) (Avalos-Te´llez et al., Reference Avalos-Te´llez, Sua´rez-Güemes, Carrillo-Casas, Herna´ndez- Castro and Me´ndez-Vilas2010). This bacterial species has been considered as an opportunistic pathogen and can cause bronchopneumonia in bottlenose dolphins (Avalos-Te´llez et al., Reference Avalos-Te´llez, Sua´rez-Güemes, Carrillo-Casas, Herna´ndez- Castro and Me´ndez-Vilas2010). Other species such as A. lwoffii, S. dysgalactiae, Achromobacter spp., Elizabethkingia spp., and A. hydrophila have been reported to be able to cause pneumonia in human beings, dolphins, and other animals (Swenshon et al., Reference Swenshon, Lammler and Siebert1998; da Silva and Pereira, Reference da Silva and Pereira2013).

Based on the literature, ample evidence is provided among several marine mammals to show the devastating effects of pneumonia. In 1813, 1836, and 1869–1870, mass mortalities of seals at Orkney were reporteldy caused by pneumonia (McConnell, Reference McConnell1985). In 1918, in Iceland, the deaths of at least 1000 common seals were reported due to severe respiratory problems (Dietz et al., Reference Dietz, Heide-Iargensen and Harkonen1989), possibly pneumonia. Similarly, in the United States, about 445 harbor seals along the New England seaboard died over a one-year period (1979–1980) due to epizootic pneumonia, though most of the seals were immature (Geraci et al., Reference Geraci, St Aubin, Barker, Webster, Hinshaw, Bean, Ruhnke, Prescott, Early, Baker, Madoff and Schooley1982, Reference Geraci, St.Aubin, Barker, Hinshaw, Webster and Rhunke1984). In 1988, the deaths of approximately 18,000 harbor seals (Phocavitulina L) living in the North Sea and Baltic Sea was recorded. The causative factor was mostly pneumonia, caused by Morbillivirus, along with a variety of opportunistic microorganisms (Giebel et al., Reference Giebel, Meier, Binder, Flossdorf, Poveda, Schmidt and Kirchhoff1991). A similar epidemic, attributed to a canine distemper-like Morbillivirus, also happened in the Soviet Union in 1987, killing thousands of Baikal seals (Phocasibirica) (Grachev et al., Reference Grachev, Kumarev, Mamaev, Zorin, Baranova, Denikina, Belikov, Petrov, Kolesnik, Kolesnik, Dorofeev, Beim, Kudelin, Nagieva and Sidorov1989); Osterhaus et al., Reference Osterhaus, Groen, UytdeHaag, Visser, Van de Bildt, Bergman and Klingeborn1989). From 1990 to 1992, about 1000 striped dolphins (S. coeruleoalba) died in the Mediterranean Sea due to pneumonia associated with dolphin Morbilivirus (DMV) (Lipscomb et al., Reference Lipscomb, Kennedy, Moffett, Krafft, Klaunberg, Lichy, Regan, Worthy and Taubenberger1996). In the Spanish Mediterranean in 1990, hundreds of striped dolphins (S. coeruleoalba) died as a result of Morbilivirus infection. Poor body condition and pneumonia were the main necropsy findings (Duignan et al., Reference Duignan, Geraci, Raga and Calzada1992). In 2007, there was a recurrence of virus which affected over 100 striped dolphins (Raga et al., Reference Raga, Banyard, Domingo, Corteyn, Van Bressem, Fernández, Aznar and Barrett2008) and 60 long-finned pilot whales (Globicephala melas) (Fernandez et al., Reference Fernandez, Esperon, Herraez, deLos, Clavel and Bernabe2008). Similarly, 28 harbor porpoises died between 1990 and 1995 on the coasts of England and Wales due to respiratory infections (Kirkwood et al., Reference Kirkwood, Bennett, Jepson, Kuiken, Simpson and Baker1997). Mortality by pneumonia in marine mammals is caused not only in the wild but also in oceanaria (Ridgway, Reference Ridgway1979). Still, pneumonia, which can be caused by viruses or bacteria, is the leading cause of death in dolphins throughout the world (Rubio-Guerri et al., Reference Rubio-Guerri, Melero, Esperón, Bellière, Arbelo, Crespo, Sierra, García-Párraga and Sánchez-Vizcaíno2013; Venn-Watson et al., Reference Venn-Watson, Colegrove, Litz, Kinsel, Terio, Saliki, Fire, Carmichael, Chevis, Hatchett, Pitchford, Tumlin, Field, Smith, Ewing, Fauquier, Lovewell, Whitehead, Rotstein, McFee, Fougeres and Rowles2015).

Vaccination of wildlife

In wild endangered animals, the application of commercial vaccine for preventing infectious diseases has received growing attention. For example, Ethiopian wolves (Canis simensis) (Randall et al., Reference Randall, Williams, Kuzmin, Rupprecht, Tallents, Tefera, Argaw, Shiferaw, Knobel, Sillero-Zubiri and Laurenson2004; Stewart, Reference Stewart2009) and foxes (Brochier et al., Reference Brochier, Kieny, Costy, Coppens, Bauduin, Lecocq, Languet, Chappuis, Desmettre, Afiademanyo, Libois and Pastoret1991) have been vaccinated with the rabies vaccine, gorillas (Gorilla beringei beringei) against measles (Whittier et al., Reference Whittier, Nutter and Stoskopf2001), and California condors (Gymnogyps californianus) against the West Nile virus (Chang et al., Reference Chang, Davis, Stringfield and Lutz2007). Recent advances in molecular technologies have enabled us to develop more efficacious and safer vaccines, specifically for wildlife species. In addition, better mass distribution strategies have been developed (Rupprecht et al., Reference Rupprecht, Hanlon and Slate2004). Recently, the National Wildlife Health Center has designed and tested several vaccines with the purpose of protecting several endangered species (Brand, Reference Brand2013). The primary objective of vaccinating a population is to mitigate an infectious disease (Anderson and May, Reference Anderson and May1992). It is important to vaccinate a majority of individuals in a population. However, this is difficult to achieve in endangered wildlife and in some cases impractical (Woodroffe, Reference Woodroffe2001). However, a disease outbreak can threaten a population even if an effective vaccine exists (Daszak et al., Reference Daszak, Cunningham and Hyatt2000; Woodroffe et al., Reference Woodroffe, Cleaveland, Courtenay, Laurenson, Artois, Macdonald and Sillero-Zubiri2004). To some extent, wildlife can tolerate limited outbreaks of infectious diseases, but large outbreaks can put a population at risk of extinction (Haydon et al., Reference Haydon, Laurenson and Sillero-Zubiri2002; Vial et al., Reference Vial, Cleaveland, Rasmussen and Haydon2006). Therefore, for ethical, economic, and logistic reasons, the use of effective, safe, and targeted vaccination could be used to curtail the most damaging and largest outbreaks, while decreasing the proportion of individuals required to be vaccinated (Haydon et al., Reference Haydon, Randall, Matthews, Knobel, Tallents, Gravenor, Williams, Pollinger, Cleaveland, Woolhouse, Sillero-Zubiri, Marino, Macdonald and Laurenson2006). Preventive vaccination of an animal reservoir can lessen the frequency of stochastic spill-over infections into wildlife (Daszak et al., Reference Daszak, Cunningham and Hyatt2000). Less invasive, reactive and targeted low-coverage vaccination strategies enhance the long-term existence of endangered wildlife, by curtailing infectious disease outbreaks. Still, research is required for the development of vaccine delivery methods and for cost-effective advice for policy-makers and conservation practitioners to develop contingency plans (Knobel et al., Reference Knobel, Liebenberg and du Toit2003; Haydon et al., Reference Haydon, Randall, Matthews, Knobel, Tallents, Gravenor, Williams, Pollinger, Cleaveland, Woolhouse, Sillero-Zubiri, Marino, Macdonald and Laurenson2006).

Vaccination of marine mammals

Pinniped and cetacean species are exposed to various pathogens, and active immunization is the best means to provide protection against infectious diseases. Still, there are no vaccines licensed for use in pinniped and cetacean species (Vaughan et al., Reference Vaughan, Del Crew, Hermanson, Wloch, Riffenburgh, Smith and Van Bonn2007). In cetaceans, Morbillivirus (Paramyxoviridae) is considered a significant cause of mortality and disease outbreaks around the world (de Swart et al., Reference de Swart, Harder, Ross, Vos and Osterhaus1995). Marine mammals are often vaccinated during a rehabilitation setting to protect them during their recovery and after their release (Visser et al., Reference Visser, vd Bildt, Brugge, Reijnders, Vedder, Kuiper, de Vries, Groen, Walvoort and UytdeHaag1989; Hughes et al., Reference Hughes, Carter, Robinson, Clarke and Clarke1992). However, during a 1988 phocid distemper virus (PDV) epidemic, commercially available attenuated canine distemper virus (CDV) vaccine was successfully used to immunize harbor and grey seals. Vaccinated pregnant grey seals were even able to transfer antibodies to their pups (Carter et al., Reference Carter, Hughes, Taylor and Bell1992; Hughes et al., Reference Hughes, Carter, Robinson, Clarke and Clarke1992). In 2007, for the first time, a DNA vaccine encoding two DMV proteins was inoculated into the bottlenose dolphin. All the vaccinated animals vaccine-specific cellular and humoral responses occurred in all the vaccinated animals (Vaughan et al., Reference Vaughan, Del Crew, Hermanson, Wloch, Riffenburgh, Smith and Van Bonn2007). Unfortunately, still no vaccines are available for the critically endangered and fragmented populations of freshwater cetaceans, including YFPs, Indus River dolphins, Ganges River dolphin and others, although their mortality is very high in their natural environment, which might be due to infectious diseases, especially pneumonia. Recent studies have confirmed chronic infections in the wild versus semi-natural free-ranging and captive YFPs (Nabi et al., Reference Nabi, Hao, Zeng, Jinsong, McLaughlin and Wang2017a, Reference Nabi, Hao, Zeng and Wangb). This is probably also true in the case of the Indus River dolphin and Ganges River dolphin, as both the Indus and Ganga Rivers are highly polluted. Unfortunately, no detailed physiological studies are available for these species. YFPs are regularly monitored and assessed physiologically, especially in the Wuhan Baiji Dolphinarium and Poyang Lake. Anthropometric data, ultrasonography, blood, milk, and blow-hole samples are taken for various research purposes (Nabi et al., Reference Nabi, Hao, Zeng, Jinsong, McLaughlin and Wang2017a, Reference Nabi, Hao, Zeng and Wangb). Injecting pneumonia vaccines during these assessment periods would likely boost the immunity and ultimate survival of the animals. Similarly, approximately 70% of the Indus River dolphins are confined to a short 190 km segment of the Indus River (Braulik et al., Reference Braulik, Uzma, Masood and Randall2015b). These animals could be easily caught, physiologically assessed, and injected with a pneumonia vaccine. The Hawaiian Monk Seal Research Program, a first-ever species-wide vaccination program for a free-ranging pinniped, has effectively protected approximately half of the population and is close to achieving the desired level herd immunity (Dunagan, Reference Dunagan2019). The success of this program can give us hope for the conservation of other aquatic mammals, especially endangered cetaceans.

Role of genomics in vaccination

Recent advances in the genomics era have altered the paradigm of vaccine development from a microbiological to a sequence-based approach. Genomics, structural genomics, immunomics, proteomics, metabolomics, and transcriptomics are being utilized to investigate the mechanism of pathogenesis, identify new targets, design new vaccines, and to predict their efficacy in an individual. The new genome-based approaches and ever-growing body of genomic data will possibly play a crucial role in developing a timely vaccine against emerging infectious diseases (Seib et al., Reference Seib, Dougan and Rappuoli2009). Genomics, through smart identification and design of targets, will also hopefully reduce the time required for pre-licensure clinical trials which are required to investigate immunogenicity, safety, and efficacy of a vaccine (Seib et al., Reference Seib, Dougan and Rappuoli2009). At present, 582 microbial genomes have been sequenced and the sequencing of over 1733 is in progress (Kaushik and Sehgal, Reference Kaushik and Sehgal2008). This could help us in investigating virulence proteins that could be potential vaccine candidates. Furthermore, a new technology called ‘ANTIGENome’ which combines the power of serological antigen identification and full genome coverage (Etz et al., Reference Etz, Minh, Henics, Dryla, Winkler, Triska, Boyd, Söllner, Schmidt, von Ahsen, Buschle, Gill, Kolonay, Khalak, Fraser, von Gabain, Nagy and Meinke2002) could be used to directly validate antigens without the need for recombinant protein expression. This technology has been used for several bacterial pathogens of the genera Streptococcus and Staphylococcus (Meinke et al., Reference Meinke, Henics, Hanner, Minh and Nagy2005; Giefing et al., Reference Giefing, Meinke, Hanner, Henics, Bui, Gelbmann, Lundberg, Senn, Schunn, Habel, Henriques-Normark, Ortqvist, Kalin, von Gabain and Nagy2008) as well as Klebsiella pneumoniae (Lundberg et al., Reference Lundberg, Senn, Schüler, Meinke and Hanner2013). Most importantly, Pan Genomics technology can identify evolutionarily stable and highly conserved protein candidate vaccines that target all serotypes and strains of a given pathogen and reduce the risk of replacement disease (Muzzi et al., Reference Muzzi, Masignani and Rappuoli2007). Furthermore, the CRISPR (clustered regularly interspaced short palindromic sequences) technology can be used for the synthesis of Gene-Deleted vaccines with a higher target specificity (Hsu et al., Reference Hsu, Lander and Zhang2014). It is, therefore, possible in the future to develop more rational, effective, and safer vaccines through the integration of these unique and novel strategies.

Major challenges

Due to their aquatic nature, vaccination in free-living cetacean species is logistically difficult. Further, the use of attenuated live vaccines is prohibited because of the potential risk of disease to vaccinated animals and due to the potential for spread to in-contact animals (Carpenter et al., Reference Carpenter, Appel, Erickson and Novilla1976; Itakura et al., Reference Itakura, Nakamura, Nakatsuka and Goto1979). The route of vaccine administration by injection, and the requirement of a booster shots when using inactivated vaccines, further complicates vaccination in free-living cetaceans (Duignan et al., Reference Duignan, Van Bressem, Baker, Barbieri, Colegrove, De Guise, de Swart, Di Guardo, Dobson, Duprex, Early, Fauquier, Goldstein, Goodman, Grenfell, Groch, Gulland, Hall, Jensen, Lamy, Matassa, Mazzariol, Morris, Nielsen, Rotstein, Rowles, Saliki, Siebert, Waltzek and Wellehan2014). The vaccination plan includes three elements, which are vaccine selection, testing of the vaccine on captive animals for safety and efficacy, and mass vaccination of free-living populations. Furthermore, it has not yet resolved whether to: (1) vaccinate only in response to an outbreak; (2) conduct prophylactic vaccination; or (3) combine both approaches (Itakura et al., Reference Itakura, Nakamura, Nakatsuka and Goto1979).