Acknowledgments We would like to thank Jorge Dominguez and David Medel for preparation of plant material and fungal strains, and Elena Zafra for microsatellite amplification. We would also like to express our gratitude to the Spanish Elm Breeding and Conservation Programme for supporting this study. This research was funded by the Ministerio de Agricultura, Alimentación y Medio Ambiente (MAGRAMA) and the Spanish National Research Plan (AGL2012-35580 and AGL2015-66925-R MINECO/FEDER, UE). P.P. acknowledges funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement PIEF-GA-2013-627761. ; Wilt diseases caused by vascular pathogens include some of the most damaging stresses affecting trees. Dutch elm disease (DED), caused by the fungus Ophiostoma novo-ulmi, destroyed most of North American and European elm populations in the 20th century. The highly susceptible English elm, also known as Atinian clone, suffered the highest mortality rates during the last pandemic event, probably due to its lack of genetic diversity. To study the DED pathosystem, we inoculated English elm ramets with O. novo-ulmi and evaluated xylem anatomy, molecular response, and disease symptoms. The high DED susceptibility of the clone was linked to xylem structure. The transcript levels changed significantly for 1,696 genes during O. novo-ulmi invasion. Genes covering different steps of the plant immune system were identified, many of which showed homology with Arabidopsis thaliana genes involved in systemic acquired resistance. Induction of several pathogenesis-related proteins and repression of fasciclin-like arabinogalactan proteins and other cell wall biosynthesis pathways evidence unbalanced costs between growth and defence mechanisms far from the inoculation point. This study sheds light on elm molecular defence mechanisms against DED ; Depto. de Genética, Fisiología y Microbiología ; Fac. de Ciencias Biológicas ; TRUE ; unpub