Simple SummaryInadequate oxygen saturation, or hypoxia, belongs to one of the critical stress factors in intensive aquaculture. Exposure of fish to low oxygen levels over prolonged periods substantially affects their well-being and immune competence, resulting in increased disease susceptibility and consequent economic losses. In this interdisciplinary research, we aimed to provide a deeper understanding of the effect of chronic low oxygen saturation on pikeperch farmed in recirculating aquaculture systems. The obtained data offer unprecedented insights into the changes in the immunocompetence of studied fish and suggest high robustness of this new aquaculture species to the stress factors of intensive aquaculture.Inadequate oxygen saturation can induce stress responses in fish and further affect their immunity. Pikeperch, recently introduced in intensive aquaculture, is suggested to be reared at nearly 100% DO (dissolved oxygen), yet this recommendation can be compromised by several factors including the water temperature, stocking densities or low circulation. Herein, we aimed to investigate the effect of low oxygen saturation of 40% DO (±3.2 mg/L) over 28 days on pikeperch farmed in recirculating aquaculture systems. The obtained data suggest that—although the standard blood and health parameters did not reveal any significant differences at any timepoint—the flow cytometric analysis identified a slightly decreased proportion of lymphocytes in the HK (head kidney) of fish exposed to hypoxia. This has been complemented by marginally downregulated expression of investigated immune and stress genes in HK and liver (including FTH1, HIF1A and NR3C1). Additionally, in the model of acute peritoneal inflammation induced with inactivated Aeromonas hydrophila, we observed a striking dichotomy in the sensitivity to the low DO between innate and adaptive immunity. Thus, while the mobilization of myeloid cells from HK to blood, spleen and peritoneal cavity, underlined by changes in the expression of key proinflammatory cytokines (including MPO, IL1B and TNF) was not influenced by the low DO, hypoxia impaired the influx of lymphocytes to the peritoneal niche in the later phases of the immune reaction. Taken together, our data suggest high robustness of pikeperch towards the low oxygen saturation and further encourage its introduction to the intensive aquaculture systems.