| Summary: | During diving, Weddell seals ( Leptonychotes weddellii ) experience repeated hypoxemia. To mediate hypoxic tissue damage, Weddell seals employ vasoconstriction favoring vital organs (e.g. brain, lung, adrenals) resulting in reduced oxygen delivery to visceral and peripheral tissues. Weddell seals therefore experience periods of local ischemia associated with vasoconstriction followed by reoxygenation and return of perfusion at the surface. Ischemia‐reperfusion injury (IRI) is the expected result from reduced blood flow and localized hypoxia, followed by reoxygenation and reperfusion. A typical human response to IRI induces inflammation. We studied the inflammatory response of Weddell seals to determine whether its downregulation could be a mechanism by which seals avoid hypoxic and IRI injury. Weddell seal white blood cells (n=12) demonstrate a reduced immune reaction (mean ± stdev 247± 200 fold induction of IL‐6 from baseline) compared to human monocytes (n=6 replicates, THP‐1 cells 3091 ± 1126 fold IL‐6 induction, t‐test p<0.0001) when exposed to an inflammatory stimulus in vitro (10 ng/mL lipopolysaccharide). To evaluate species differences in gene pathways associated with the immune response, we conducted RNA‐seq and identified distinct transcriptomic profiles between species. We next evaluated the inflammatory response of Weddell seal primary cells (monocytes and pulmonary endothelial cells) resulting from hypoxia and reoxygenation. By simulating this natural stressor, we aim to discover whether the response of immune cells is an important component of molecular protection against IRI inflammatory sequelae in diving seals.
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