Transcriptomic insights into the immune responses of the lung and muscle of non-healthy harbor porpoises (

Introduction: The harbor porpoise populations of the North and Baltic Seas are highly impacted by human activities, including underwater-radiated noise, fisheries and pollution. These cumulative stressors can have various detrimental effects, such as reduced foraging success, altered behavior and an impaired immune system. Harbor porpoises especially suffer from diseases of the respiratory tract which are partly caused or exacerbated by high parasitic prevalence in the lungs that may ultimately affect diving ability and competitiveness due to insufficient oxygen uptake and supply to the locomotor musculature. Methods: To investigate pathophysiological mechanisms and potential compensatory adaptations to pathogenic insults, we employed transcriptomics and compared lungs and muscles of harbor porpoises with compromised respiratory health to healthy individuals. Additionally, a Results and Discussion: Non-healthy harbor porpoises showed a distinct host-pathogen defense reaction in the lung, suggesting similarities to immune responses of humans suffering from lung diseases, which may be conserved along the mammalian lineage despite vastly different habitats. However, the lung transcriptomes did not indicate a Th2 immune response which is typically activated upon parasitic insults. Severely infected harbor porpoises may be overwhelmed or weakened by prolonged parasitic exposure and immune activation, possibly affecting simultaneous pathogenic clearance and tissue repair. The muscles of non-healthy harbor porpoises exhibited enhanced stress signaling and tightly regulated tissue degradation/regeneration, potentially reflecting a chronic inflammation state. Higher expression of hypoxia- and oxidative stress-associated transcripts in the muscle were consistent with hypoxia-induced transcriptional patterns and suggest a systemic pathological challenge. The