Evolutionary Mechanisms of Coagulation Factors in Cetaceans During Aquatic Adaptation.

Cetaceans exhibit rapid wound healing in marine environments characterized by hypoxia and high pathogen loads, yet the adaptive mechanisms underlying their coagulation system remain poorly understood. We integrated evolutionary analyses with functional experiments to elucidate the molecular basis of specialized coagulation in cetaceans. Routine coagulation tests performed on Tursiops truncatus (n = 3) and Bos taurus (n = 3) showed that T. truncatus plasma exhibited significantly shortened prothrombin time and thrombin time, as well as prolonged activated partial thromboplastin time (APTT). Evolutionary analyses revealed that 18 genes were under positive selection in cetaceans, with F11 showing accelerated evolution and lineage-specific amino acid substitutions. APTT mixing assays showed that bovine plasma shortened the prolonged APTT of T. truncatus plasma, suggesting that differences in intrinsic pathway components may contribute to the cetacean coagulation phenotype. Compared to B. taurus, Tursiops truncatus coagulation factor VII increased protein abundance, while factor V abundance was reduced. Plasma proteomic analysis further suggested that differentially expressed proteins were enriched in pathways related to lipid metabolism, the coagulation cascade, and antiviral responses. In conclusion, the cetacean coagulation system has undergone adaptive evolution at both genetic and protein levels. Key amino acid changes such as coagulation factor XI (FXI) and coagulation factor VII (FVII) may optimize coagulation balance by modulating protein interaction strengths; the conserved evolution and increased plasma abundance of PLG may indicate a potential contribution of fibrinolytic regulation to cetacean coagulation balance. This study provides coagulation biology evidence for physiological adaptation in aquatic mammals.