Integrated Metabolic, Oxidative, Inflammatory, and Mammary Health Signatures Characterize Low Body Condition Score in Dairy Cows

Body condition score (BCS) is widely used to assess the energy status of dairy cows, yet its relationship with coordinated metabolic and immune responses during early lactation remains incompletely understood. The aim of this study was to characterize the physiological profile associated with low BCS using biomarkers of energy metabolism, hepatic function, oxidative status, inflammation, mammary gland health, milk production, and milk composition. A total of 580 Polish Holstein–Friesian cows in early lactation were classified into four BCS categories and evaluated using univariate and multivariate statistical approaches, including composite physiological indices and partial least squares discriminant analysis (PLS-DA). Cows with the lowest BCS (2.0–2.5) exhibited marked lipid mobilization and hepatic stress, reflected by higher concentrations of non-esterified fatty acids, β-hydroxybutyrate, aspartate aminotransferase, and gamma-glutamyl transferase (all p < 0.001). These changes were accompanied by increased oxidative stress, elevated inflammatory activity, alterations in mammary gland biomarkers, and changes in selected milk traits. Composite physiological indices consistently differentiated low-BCS cows from the remaining groups, while PLS-DA identified a distinct biomarker profile associated with low body condition. Among the evaluated variables, interleukin-8 showed the greatest contribution to class discrimination, ranking above conventional metabolic biomarkers in the multivariate analysis. The results indicate that low body condition score is associated with coordinated alterations involving metabolism, liver function, oxidative balance, inflammation, and mammary gland responses rather than isolated metabolic disturbances. The proposed composite physiological indices and the Integrated Low-BCS Phenotype Score (ILBPS) provide an integrative framework for characterizing the physiological phenotype associated with low body condition during early lactation. Prospective longitudinal studies are required to determine whether these biomarkers and composite indices have prognostic value for subsequent metabolic or clinical outcomes.