Multiple changes have been identified previously in

dolphins during feeding and fasting states. Dolphins fasted overnight have higher serum glucose, platelets, gamma-glutamyl transpeptidase, and alkaline phosphatase; shifts toward a metabolic acidotic state; and lower serum uric acid compared to those that had recently fed (Venn-Watson and Ridgway 2007). These changes mimicked those found in people with and without diabetes (Androgue et al. 1982, Maxwell et al. 1986, Chitre and Valskar 1988, Andre et al. 2006, Nan et al. 2007). Indeed, dolphins have a diabetes-like metabolism, in which ingested sugars or high-protein fish meals lead to a sustained hyperglycemia lasting 5–10 h (Ridgway et al. 1970, Venn-Watson et al. 2011). Interestingly, endogenous nitric oxide can be impaired in people with diabetes, including reduced nitric oxide Small molecule library nmr availability (Honing et al. 1998). The differences in nitric oxide levels found in the breath of fed vs. fasted dolphins should be further MAPK inhibitor evaluated to better understand the impacts of the dolphin’s high protein diet and their diabetes-like metabolism.

A primary driver of the current study was to assess the use of breath analysis as a noninvasive indicator of cetacean health, including detection of early stages of pneumonia. In addition to general evaluation of metabolism and lung function, volatiles in the breath have been employed as “fingerprints” for detecting disease in other animal models. Carbon

dioxide, oxygen, nitric oxide, carbon monoxide, hydrogen sulfide (and other sulfides), 4-Aminobutyrate aminotransferase acetone and other volatiles may be useful in diagnosis of lung injury and numerous metabolic or infectious diseases (Phillips 1992, Kharitonov et al., 1996, Phillips et al. 2003). The successful detection of NO in exhaled dolphin breath opens the possibility of using NO as a clinically relevant diagnostic test. In this study, a dolphin with chronic disease, including gastrointestinal disease of unconfirmed origin and a Mycoplasma-associated pneumonia, had higher postprandial exhaled NO compared to postprandial breath from healthy controls. There were no differences in exhaled NO, however, when comparing another case dolphin with chronic coccidiodomycosis with healthy controls. Reasons for this difference may be the severity of infection or inflammation, organ systems involved, or pathogen. Further studies are needed to better understand under what conditions NO may successfully detect disease in dolphins and why, in this study, significant differences between the case dolphin and healthy control dolphins were not apparent until postprandial samples were compared. Digestive state and disease detection should be considered when examining dolphins for different diseases. Standardized methodologies for sample collection will continue to be needed if NO in breath is to be used for illness detection and comparability across populations and time.