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Bats are unique among mammals in their ability to perform sustained, self-powered flight, a highly energy-demanding activity that places continuous stress on the heart. This study aimed to investigate the metabolic mechanisms that support cardiac resilience in the Egyptian fruit bat (Rousettus aegyptiacus). Using integrated high-resolution 1H NMR spectroscopy, targeted LC-MS/MS profiling, and in silico flux balance modelling (CardioNet), we compared cardiac tissue from adult fruit bats to C57BL/6J mice (n=4/group).Metabolomic analysis revealed that bat hearts have depleted glycogen and creatine stores, alongside elevated AMP, reduced NAD(P)+ redox equivalents, and significantly increased lipid metabolites. In silico modelling predicted increased oxidative phosphorylation and fatty acid β-oxidation in bats, particularly during flight. Across simulated activity states (roosting, night activity, flight) oxygen consumption and ATP demand scaled with activity, with a pronounced reliance on lipid oxidation. Glucose utilization was low in all conditions, while ketone body oxidation increased during lower-activity states.Our findings demonstrate that Egyptian fruit bats possess a metabolically flexible and lipid-focused cardiac profile that enables them to meet the intense energetic demands of flight without developing cardiac pathology. These adaptations provide novel insight into energy-efficient cardiac performance and may offer translational relevance for understanding human cardiac metabolism under stress.Reference Karlstaedt A, Cullen F, Drinkwater R, Kim K, Young M, Rossiter SJ, Aksentijevic D. Bat power-metabolic profiling of the Egyptian fruit bat Rousettus aegyptiacus reveals distinctive cardiac adaptations. bioRxiv 2025. doi: https://doi.org/10.1101/2025.04.16.649087