Aggressive behavior is ubiquitous across many contexts, including defense of territories, mates, and offspring. For decades, researchers have detailed the effect of aggressive behavior on physiology, but our understanding of these mechanisms in females lags behind that of males, despite the fact that female aggression is widespread, particularly in the context of maternal defense of eggs or offspring (i.e., maternal aggression). Here, we measured effects of a social challenge on brain gene expression in free-living incubating females. We hypothesized that the social challenge would generate at least one of three transcriptomic effects: (1) sensitizing the brain to otherwise low levels of sex steroids, (2) changing other neuroendocrine signaling pathways associated with social behavior (e.g., dopamine), or (3) broad shifts related to metabolism or immune function. We tested these hypotheses in incubating female tree swallows (Tachycineta bicolor), exposing 10 females to a 30-min simulated territorial intrusion, which elicited maternal aggression. After this challenge, we measured neural gene expression via RNA-seq and compared gene expression to 10 unchallenged controls. We saw no global treatment effect on gene expression. However, within the experimental group, more maternal aggression was correlated with upregulation of genes associated with immune activation and downregulation of genes associated with synaptic plasticity. Though more research is needed to understand the downstream effects of these transcriptional differences, our findings generate key questions about how the brain responds to social challenges across different contexts.