In a respiratory-infection-model with the avian influenza A H9N2 virus we studied lung and splenic immune reactions in chickens using a recently developed 5K chicken immuno-microarray. Groups of chickens were either mock-immunized (referred to as non-immune), vaccinated with inactivated viral antigen only (immune) or with viral antigen in a water-in-oil (W/O) immunopotentiator (immune potentiated). Three weeks after vaccination all animals were given a respiratory infection. Immune potentiated birds developed inhibitory antiviral antibodies, showed minimal lung histopathology and no detectable viral sequences, while non-immune animals showed microscopic immunopathology and detectable virus. Immune birds, receiving antigen in saline only, showed minimal microscopic histopathology, and intermediate levels of virus detection. These classical features in the different groups were mirrored by overlapping or specific mRNA gene expression profiles in lungs and spleen using microarray analysis. To our knowledge this is the first study demonstrating pneumonia-associated lung pathology of the low pathogenic avian influenza H9N2 virus. Our data provide insights into the molecular interaction of this virus with its natural host when naive or primed by vaccination.