Mallard (Anas platyrhynchos) Interleukin-4 (IL-4) is a Th2-associated cytokine produced primarily by CD4⁺ T helper–like cells and other type 2 immune populations, where it plays a central role in regulating humoral immunity and modulating inflammatory responses in this important wild waterfowl species. IL-4 signals through receptor complexes containing IL-4Rα and associated receptor chains, activating JAK/STAT6 pathways that promote B-cell proliferation, antibody production (including IgY and mucosal IgA responses), and suppression of Th1-associated cytokines such as IFN-γ. In mallards, which are natural reservoir hosts for avian influenza viruses (AIV), IL-4 is particularly relevant in shaping the balance between antibody-mediated responses and cell-mediated antiviral immunity, potentially contributing to effective viral control with minimal clinical disease. IL-4 may also play roles in responses to parasitic infections and enteric pathogens encountered in aquatic environments, supporting mucosal repair and immune tolerance. Dysregulated IL-4 expression could influence viral shedding dynamics or susceptibility to secondary infections. As a biomarker of Th2 immune polarization, mallard IL-4 is important in studies of avian influenza ecology, vaccine responses in domestic waterfowl, and host–pathogen co-evolution. Characterization of IL-4 in this species enhances understanding of immune regulation in reservoir hosts and provides comparative insight into Th1/Th2 balance across avian and mammalian species.