Objective: Some marine mammals of the order pinniped and cetacean can dive for long durations to forage for food and travel over distances. During these extended dives both pinnipeds and cetaceans experience extreme tissue hypoxia. Numerous adaptations have evolved to allow these species to effciently deliver and utilize oxygen (O2). One genetic difference, which our laboratory has proposed to play an important role in O2 transport effciency in modern hominids, is the inactivation of the CMP-Neu5AC hydroxylase (CMAH) gene. Pinnipeds inactivated Cmah ~ 40 million years ago but, cetaceans still express this N-glycan modifying enzyme. CMAH converts the sialic acid, N-acetylneuraminic acid (Neu5Ac), to its hydroxylated form, N-glycolylneuraminic acid (Neu5Gc). These sialic acids are located at the end of branched sugar chains on the surface of cell membranes. As a result, a change in composition could affect cell membrane charge and hydrophobicity, as well as potentially alter O2 diffusion laterally or across cell membranes. Hypothesis: In this study we hypothesized that O2 transfer from hemoglobin (Hb) in red blood cells (RBCs) to myoglobin (Mb) would differ between cetaceans (CMAH+) and pinnipeds (CMAH-). Methods: This hypothesis was tested using optical absorption spectroscopy to measure O2 exchange between oxygenated Hb in RBC and deoxygenated Mb collected in several species of mustelids and pinniped (CA sea otter, CA sea lion, and walrus) and cetaceans (Bottlenose Dolphin, Beluga, and Orca). Measurements of cell diameters (diffusion length) were also measured. Results: The mean oxygen transfer (O2D/A410) was 47% lower in pinnipeds than cetaceans (p<0.01). The amount of O2 transferred in cetaceans increased with longer reported maximal dive durations. There was a trend for overall RBC diameters to be larger in cetaceans than pinnipeds (p=0.054). Summary: The RBC O2 transfer data in these hypoxia tolerant marine mammals suggest a transfer mechanism that is more effcient in cetaceans in a normoxic environment. Conclusions: More effcient oxygen transfer in cetaceans, who retained the Cmah gene, compared to pinnipeds and mustelids, who did not retain the Cmah gene, suggests that the gene knockout may not be the only factor that facilitates delivery of O2 in these marine mammals. A trend for larger RBC diameters in cetaceans than pinnipeds also suggests that diffusion length is not a main contributing factor. Future experiments to measure oxygen transfer from RBC O2-Hb to Mb under different O2 environments are needed to more closely model what may occur during long duration dives. NSF1929325. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.