Physiological resiliency in diving mammals: Insights on hypoxia protection using the Krogh principle to understand COVID-19 symptoms.

Sequential diving by wild marine mammals results in a lifetime of rapid physiological transitions between lung collapse-reinflation, bradycardia-tachycardia, vasoconstriction-vasodilation, and oxygen store depletion-restoration. The result is a cycle of normoxia and hypoxia in which blood oxygen partial pressures can decline to <20-30 mmHg during a dive, a level considered injurious to oxygen-dependent human tissues (i.e., brain, heart). Safeguards in the form of enhanced on-board oxygen stores, selective oxygen transport, and unique tissue buffering capacities enable marine-adapted mammals to maintain physiological homeostasis and energy metabolism even when breathing and pulmonary gas exchange cease. This stands in stark contrast to the vulnerability of oxygen-sensitive tissues in humans that may undergo irreversible damage within minutes of ischemia and tissue hypoxia. Recently, these differences in protection against hypoxic injury have become evident in the systemic, multi-organ physiological failure during COVID-19 infection in humans. Prolonged recoveries in some patients have led to delays in the return to normal exercise levels and cognitive function even months later. Rather than a single solution to this problem, we find that marine mammals rely on a unique, integrative assemblage of protections to avoid the deleterious impacts of hypoxia on tissues. Built across evolutionary time, these solutions provide a natural template for identifying the potential for tissue damage when oxygen is lacking, and for guiding management decisions to support oxygen-deprived tissues in other mammalian species, including humans, challenged by hypoxia.