Frequent replanting causes biotic stress due to an altered soil and rhizosphere biome and results in apple replant disease (ARD). The disease is expressed by diminished growth and negatively affects fruit yield and quality. Recent studies aiming at understanding ARD on a molecular level showed that ARD affected plants suffer from oxidative stress. Genes involved in secondary metabolism reactions play an important role in the molecular ARD response of roots. Although the root system has to endure the biotic stress attack in the first place, severe symptoms of ARD can be visualized on aboveground plant parts. The objective of this study was to examine the transcriptomic response of leaves representing the metabolically active aboveground parts of ARD challenged apple plants and to compare results with existing data for roots to generate a more complete picture of ARD affected molecular reactions. For this, biotic stress response genes induced by ARD in roots were studied in RT-qPCR analyses using leaves of ARD sensitive ‘M26’ plants grown in two ARD soils, also in a time-dependent approach. Furthermore, an RNA sequencing approach employing MACE (massive analysis of cDNA ends) for transcriptome profiling was performed in order to identify further leaf specific candidate genes. RT-qPCR analyses did not reveal major differences in root candidate gene expression, but MACE indicated the upregulation of common biotic stress response genes. However, potential systemic oxidative stress occurred and ‘M26’ plants did not develop an effective defense response to ARD.