Prepartum Heat Stress Dysregulates Immune Resilience in Postpartum Dairy Cows

Increasing environmental temperatures pose a major challenge to animal welfare by inducing heat stress and increasing the incidence of disease. Immune resilience is essential for maintaining animal health; however, the mechanisms linking heat stress to immune dysfunction and disease remain unclear. We hypothesized that prepartum heat stress would result in persistent disruption of immune resilience after calving when cows were no longer heat stressed. During summer, non-lactating, pregnant cows were subjected to either prepartum cooling (fans, water soakers, and shade; n = 31) or heat stress (shade only; n = 31) for the last 46 days of gestation. After calving, all cows received cooling. Postpartum health, peripheral blood, and endometrial samples were evaluated up to 21 days postpartum. Prepartum heat stress increased the incidence of postpartum diseases compared to cooled cows, with little change to the uterine microbiome. Prepartum heat stress increased postpartum white blood cell counts and mean platelet volume, while lipopolysaccharide-stimulated expression of CXCL8, IL1B, and TNF tended to be attenuated in whole blood. Interestingly, prepartum heat stress increased lipopolysaccharide-stimulated secretion of IL-6 and IL-8 in whole blood. In parallel, prepartum heat stress induced mild but persistent changes to the postpartum endometrial transcriptome associated with immunological pathways. Furthermore, prepartum heat stress attenuated basal expression of CXCL8, IL6, and TNF in cultured endometrial cells. Collectively, these findings demonstrate that prepartum heat stress increases disease incidence and disrupts peripheral and endometrial immune resilience independent of changes to the microbiome in postpartum cows.