F Fiorani, H Carignano, A M Pardo, D P Moore, P M Corva
Neospora caninum is a leading cause of abortion in cattle worldwide, yet the role of host genetic background in early immune responses remains incompletely understood. This study compared early transcriptional responses to N. caninum infection in two cattle breeds with contrasting selection histories using a controlled in vivo model. Fourteen-month-old, non-pregnant Argentine Creole and Holstein heifers (n = 8 per breed) were intravenously inoculated with live N. caninum tachyzoites or mock-treated. Peripheral blood mononuclear cells were collected at 7 days post-infection and analyzed by bulk RNA sequencing across the following contrasts: Uninfected breeds, Holstein infection, Argentine Creole infection and infected breeds, capturing the transition from innate immune sensing to early cellular activation. Transcriptomic variation was primarily driven by breed rather than infection status, indicating that responses to infection were deployed upon distinct baseline immune configurations. Under basal conditions, Creole heifers exhibited an interferon-enriched, immune-primed transcriptional profile, whereas Holstein heifers showed greater representation of biosynthetic and translation-related pathways. Following infection, both breeds activated canonical immune pathways; however, their responses differed in magnitude and organization. Creole heifers displayed broader transcriptional remodeling, integrating immune effector functions, lymphocyte proliferation, and trafficking-related processes. In contrast, Holstein heifers showed a more restricted response, characterized by enrichment of cell cycle and metabolic pathways. These findings indicate that host genetic background modulates baseline immune configuration and influences early transcriptional responses to N. caninum infection, providing a framework for understanding how genetic variation may contribute to differences in host-parasite interactions and disease dynamics across cattle populations.