In recent years, human activities in German waters have expanded continuously, impacting native harbour porpoise populations (Phocoena phocoena). Harbour porpoises often display severe pathological lesions in the respiratory tract, mainly caused by bacteria and parasites. Additionally, telemetry studies revealed they do not use their complete lung volume. It has not been studied whether this is due to the pathological lung lesions reducing the oxygen uptake of the porpoises, impairing their diving ability. Using multi-omics, this study aims to investigate whether harbour porpoises developed compensatory molecular adaptations to an inadequate oxygen uptake, therefore staying competitive. Multi-omics of non-healthy harbour porpoise lungs revealed an enhanced response to reactive oxygen species such as hydrogen peroxide known to cause oxidative stress. Potent detoxifiers such as multiple S100A genes and glutathione peroxidases were upregulated and highly abundant. Also, an extensive activation of immune system responses against microbes, bacteria and other organisms was identified. Elevated chemotaxis hints at a swift aggregation to the site of infection or inflammation, while mucosal immune responses and transport suggests quick pathogen removal. Moreover, upregulation of surfactant proteins may aid in immunoprotection and respiration of the impaired lung tissue. Reduced cell adhesion, tissue remodelling and apoptosis execution may avoid further damage by suspending cell-cell interactions and cell death. These insights suggest a comprehensive immune response to pathogens, inflammation and reaction to ROS, enabling specific functional analyses of newly identified transcripts. Further, this study illustrates the potential of multi-omics to noninvasively advance the knowledge of marine mammal adaptations, especially to anthropogenic impacts.